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首頁> 外文學位 >Disruption of model membranes by PAMAM dendrimers and quantitative nanoscale analysis of type 1 collagen.
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Disruption of model membranes by PAMAM dendrimers and quantitative nanoscale analysis of type 1 collagen.

機譯：PAMAM樹狀聚合物破壞模型膜并進行1型膠原的定量納米級分析。

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The work presented in this thesis uses the Atomic Force Microscope (AFM) to study the properties of nano-scaled biological systems. This work is divided into two major sections. The first section uses Survanta as a model system for studying the interaction of nanoparticles with the lung lining. The second section looks at the nanoscale morphology of collagen fibrils.;Survanta forms a phase-separated bilayer when deposited onto mica. At room temperature one domain is comprised of mostly the anionic POPG in the fluid phase, while the other domain contains the zwiterionic DPPC in the gel phase. Generation 5 and 7 Poly(amidoamine) dendrimers preferentially disrupt the fluid layer. For the first time, dendrimer can be observed collecting on top of the lipid preceding removal. The location of the dendrimer is verified by phase imaging. Molecular Dynamics simulations also support that dendrimers are on top of the bilayer. These simulations show that the dendrimer deforms more when interacting with a fluid lipid bilayer. This increase in deformation is observed in AFM images through an analysis of the edge profiles of the dendrimer adhered to the surface. Finally, following removal, no dendrimer is adhered to the mica substrate. This observation, coupled with observations of the dendrimer on top of the lipid, supports that disruption is due to lipid encapsulating dendrimer and not a disruption of the interaction of lipid and substrate.;Turning to the second part of the thesis, collagen fibrils exhibit a characteristic banding pattern roughly 67 nm in spacing. A 2D Fast Fourier Transform technique has been developed to measure both the spacing and orientation of fibrils within AFM images. Computer simulations and experimental data show at least 9 D-Period repeats must be measured to minimize the potential for error. The resolution limit of the 2D-FFT technique is 0.8 nm. Large populations of fibrils from Ovine samples, exhibit a distribution of fibril spacing---significantly larger than the resolution limit---around a central mean. A distribution of spacings also exists in electron microscope images. X-Ray scattering data also shows similar sized distributions in spacing. Finally, statistical comparisons show a significant change in the distribution caused by estrogen depletion in Ovine samples.
機譯：本文提出的工作使用原子力顯微鏡（AFM）來研究納米級生物系統(tǒng)的特性。這項工作分為兩個主要部分。第一部分使用Survanta作為模型系統(tǒng)來研究納米粒子與肺內(nèi)膜的相互作用。第二部分著眼于膠原纖維的納米級形態(tài)。Survanta沉積在云母上時形成相分離的雙層。在室溫下，一個區(qū)域在液相中主要由陰離子POPG組成，而另一個區(qū)域在凝膠相中包含兩性離子DPPC。第5代和第7代聚（酰胺基胺）樹狀聚合物優(yōu)先破壞流體層。首次觀察到樹枝狀大分子在去除前聚集在脂質(zhì)之上。樹枝狀聚合物的位置通過相成像進行驗證。分子動力學模擬還支持樹枝狀聚合物位于雙層的頂部。這些模擬表明，當與流體脂質(zhì)雙層相互作用時，樹枝狀聚合物變形更多。通過分析粘附在表面上的樹枝狀聚合物的邊緣輪廓，可以在AFM圖像中觀察到這種變形的增加。最后，除去后，沒有樹狀大分子附著在云母基底上。這一觀察結果與對脂質(zhì)頂部的樹狀聚合物的觀察相結合，支持了這種破壞是由于脂質(zhì)包裹樹狀聚合物而不是對脂質(zhì)與底物之間相互作用的破壞。特征帶狀圖案的間距約為67 nm。已經(jīng)開發(fā)了2D快速傅里葉變換技術來測量AFM圖像中原纖維的間距和方向。計算機仿真和實驗數(shù)據(jù)表明，必須測量至少9個D周期重復，以最大程度地減少錯誤的可能性。 2D-FFT技術的分辨率極限為0.8 nm。來自綿羊樣品的大量原纖維在中心平均值附近顯示出原纖維間距的分布-明顯大于分離度極限。在電子顯微鏡圖像中也存在間距的分布。 X射線散射數(shù)據(jù)還顯示出類似的間距分布。最后，統(tǒng)計比較表明綿羊樣品中雌激素耗竭引起的分布發(fā)生了顯著變化。

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  • 作者

    Erickson, Blake William.;

  • 作者單位

    University of Michigan.;

  • 授予單位 University of Michigan.;
  • 學科 Biophysics General.
  • 學位 Ph.D.
  • 年度 2010
  • 頁碼 163 p.
  • 總頁數(shù) 163
  • 原文格式 PDF
  • 正文語種 eng
  • 中圖分類
  • 關鍵詞

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